CCL17 as a biomarker of premature atherosclerosis in the early development of systemic lupus erythematosus: insights from the Chinese CSTAR cohorts

Background/Objectives Although the association between accelerated atherosclerosis and systemic lupus erythematosus (SLE) patients has been established, the precise molecular mechanisms driving this progression remain unclear, and current predictive models inadequately forecast long-term atherosclerotic cardiovascular disease (ASCVD) events in this population. This study aims to elucidate the pathways underlying accelerated atherosclerosis in SLE and to identify serum biomarkers that could improve ASCVD risk prediction. Methods A prospetive screening and follow-up study has been conducted within the CSTAR cohort since 2016. 273 patients were followed up for a median of 7.15 years. Outcomes were assessed through medical record review and individual follow-up with patients or their relatives. Atherosclerotic changes were evaluated using portable pulse wave velocity (PWV) devices and carotid ultrasound. Subjects were divided based on atherosclerotic progression during follow-up (Figure 1A). Serum biomarkers associated with disease progression were identified using the Olink proteomics platform (Target 96 Cardiovascular II). To further investigate ASCVD progression in SLE, an ApoE-/- pristane-induced mouse model was established. Results The 7-year longitudinal follow-up study revealed significant findings regarding CCL17 as a biomarker of atherosclerotic progression risk. Patients with high serum CCL17 levels had significantly higher concentrations compared to those with low levels, and high CCL17 levels were associated with a lower survival probability (p = 0.0022), suggesting its role as a negative pro-atherosclerotic marker (Figure 1B-D). In vivo mouse models, SLE-AS model is with the aortic lesion area being significantly larger. Mice aorta expression of CCL17 elevated at both transcriptome and protein level (Figure 1E-G). Conclusion We identified CCL17 as an SLE-atherosclerosis-specific biomarker associated with the future development of atherosclerotic progression.